Chapter 4 - Epstein-Barr Virus and Multiple Sclerosis

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system that leads to myelin loss and progressive disability. The causes of MS are still unknown but the disease process is likely triggered by an environmental factor(s) in genetically susceptible individuals. Several different viruses have been identified as possible MS triggers but increasing evidence strongly associates Epstein-Barr virus (EBV) to MS. Epidemiological findings show that EBV infection, especially if accompanied by mononucleosis, greatly increases MS risk. Other relevant findings include the correlation between disease onset and the titer of anti-EBV antibodies in the serum. Dysregulated EBV specific T cells responses have been detected in MS, suggesting that MS patients might have a decreased ability to control EBV replication and there is also evidence of cross-reactivity between EBV antigens and myelin. The main site of EBV latency is the B cell compartment and B cell depletion therapies have been recently shown to strongly reduce disease activity in relapsing-remitting MS. Intriguingly EBV positive B cell follicles have been found in the brain of MS patients. Further, EBV has been shown to infect cell types other than B cells and these could play a role in MS pathogenesis. Despite all these findings, it is still unclear how EBV triggers MS. In this review we will summarize past literature and discuss possible mechanisms that EBV is exploiting to trigger